Purification of the Thr AK/HSDH inactivating protein will continue with the hope of attaining a homogeneous preparation with which to study the mechanism by which AK activity is lost. It will be necessary to determine whether the loss of activity is due to enzyme modification or proteolytic cleavage, whether the reaction is specific for Thr AK or is generalized, how the reaction is controlled, and how it relates to the regulation of cell metabolism. In addition to enzymologic and physical approaches, antibodies will be raised to both the Thr AK/HSDH and to the inactivating protein in order to study their interaction immuno- chemically. Efforts at isolating a genetic mutant lacking the inactivating activity will be made.